Description:
<jats:title>Abstract</jats:title><jats:p>Pancreatic cancer is the fourth leading cause of cancer‐related death in men and women in the United States. Reproductive factors and steroid hormones have been suspected risk factors for many years, but the results from epidemiologic studies to date have been inconclusive. <jats:italic>CYP17A1</jats:italic> encodes cytochrome P450c17α, an enzyme with 17α‐hydroxylase and 17,20‐lyase activities in estradiol biosynthesis. A polymorphism in the 5′UTR promoter region of <jats:italic>CYP17A1</jats:italic>‐34T/C(A1/A2) has been associated with circulating estrogens in premenopausal women and with susceptibility to breast, prostate, and endometrial cancer. Questionnaire data and germline DNA collected in a San Francisco Bay Area population‐based case‐control study of pancreatic cancer (cases = 532, controls = 1701) were used to conduct analyses of pancreatic cancer susceptibility related to the <jats:italic>CYP17A1</jats:italic> polymorphism and whether effects associated with smoking and reproductive risk factors were modified by this polymorphism. Mass spectrometry– and TaqMan‐based methods were used to determine <jats:italic>CYP17A1</jats:italic> genotypes in DNA samples from 308 cases and 964 controls. Results showed that carriers of the A2 allele (<jats:italic>vs.</jats:italic> A1/A1) were significantly less likely to have been diagnosed with pancreatic cancer (A1/A2, adjusted odds ratio (OR) = 0.77, 95% confidence interval (CI) = 0.58‐1.0; A2/A2, OR = 0.63, 95%CI = 0.42‐0.93; <jats:italic>p</jats:italic>‐trend = 0.01). ORs for <jats:italic>CYP17A1</jats:italic> genotypes did not differ by sex, but the observed inverse association was stronger in postmenopausal women. ORs for smoking and pancreatic cancer were not modified by <jats:italic>CYP17A1</jats:italic> genotype. Our results suggest that the <jats:italic>CYP17A1</jats:italic> A2 allele may be associated with a lower risk of pancreatic cancer in both men and women.</jats:p>